1. Field
The invention is concerned with the collection of human sweat for medical evaluation and is particularly directed to the providing of a new sweat collection device.
2. State of the Art
For many years it has been known that the concentrations of sodium and chloride are considerably above normal in the sweat of children suffering from cystic fibrosis of the pancreas.
In recent years, it has been common to induce sweating in a localized area of a person's body by an iontophoretic application of a drug such as pilocarpine nitrate. Under one sweat-collection method, the stimulated skin area is covered by a preweighed, salt-free, gauze pad which is held in place by a sheet of plastic sealed to the patient such that the sweat produced in the covered area is collected in the gauze pad. After approximately 45 minutes or longer the pad is quickly removed and re-weighed, after which the sweat is eluted into an aqueous solution for analysis, taking care not to allow evaporation of any of the sweat, since sweat evaporation results in artificially high concentrations of sodium and chloride.
More recently, it has been discovered that electrical conductivity and osmolality measurements of sweat are also useful for determining increased sodium and chloride concentrations. An advantage of these methods is that a much smaller volume of sweat can be used than is required by the gauze method, and it has been common practice to sealingly secure a small inverted cup over the pilocarpine-treated skin area for the collection of the secreted sweat. Sweat droplets form on the skin covered by the cup and are collected for analysis by tilting the cup and scraping the skin-contacting portions of the cup's rim across the skin to pool the droplets and force the pooled sweat into the cup. This method of collection has suffered, however, by reason of condensation on the interior of the cup, which introduces major error in the results of the analysis. Also, a large surface area of sweat is exposed when the cup is removed, thus making it necessary to work rapidly when collecting the sweat so that salt concentration will not be artificially high.
Use of a cup for sweat-collection also poses the problem of determining how much sweat will be collected, since some persons sweat much more than others. Thus, just prior to removing a cup, one is never sure whether or not a sufficient quantity of sweat has been collected.
A heated sweat cup as described in U.S. Pat. No. 4,266,556 has eliminated the serious problem of error caused by condensation. It provides an error-free sample of the patient's sweat. However, as with any cup device for collecting sweat and even though a practitioner can become very adept with practice, it is difficult to avoid loss of sweat during scraping, and error may arise from inclusion of sweat, concentrated by evaporation, that borders the area covered by the cup.
Although the heated cup must be recognized as a major advance in sweat collection devices, there has been one other negative factor connected with its use. It should be realied that the patients who are tested for cystic fibrosis are generally quite young. The iontophoresis step requires the patient to be "attached" to an electrical power source for several minutes. Use of a heated cup extends this time by some fifteen minutes more, a length of time which may seem interminable to a child.
A quite different sweat-collecting device was used early in the 1960's for experimental purposes in simultaneously measuring the rate of sweating and the salt concentration of the sweat. It is described and schematically illustrated in the June 1963 issue of "The Journal of Pediatrics", pages 855-867, in an article entitled "Studies of Salt Excretion in Sweat" by Lewis E. Gibson and Paul A. di Sant' Agnese. This device comprised a shaped, cylindrical block of transparent "Lucite" plastic, having a concave bottom surface bordered by an annular flat margin for direct application to the skin of a patient as a sweat collector. Sweat produced within the area covered by the concavity was forced into an elongate, transparent, measuring tube connected to an axial bore leading upwardly from the center of the concavity. Salt concentration of the sweat was determined by means of two electrodes extending into the axial bore in spaced relationship lengthwise of the bore to measure electrical conductivity of the sweat in the bore. Periodically, sweat was removed from the device by means of a syringe connected to a so-called "pull-off" tube that intersected the bore below the electrodes. The total sweat sample obtained by the syringe was subjected to electrical conductivity measurement to determine average conductivity and was analyzed photometrically for salt content.
This device had what the experimenters termed "dead space", which included space between the skin of the person being tested and the concave sweat-collecting surface of the device. Although this was recognized as a source of possible error in test results obtained by experimental use of the device and was taken into consideration in test calculations made, it represents a loss of sweat volume which could be serious in the routine medical laboratory use of a device of this kind.
Thus, sweat loss due to dead space ranged from 8.8 to 42.1 microliters and averaged 20.3 microliters. Since the average patient normally produces a total volume of only 50-60 microliters of sweat during an entire period of collection, losses of such magnitude cannot be regarded as insignificant. Moreover, the sweat collected under these circumstances is not representative, since the rate of sweat production decreases with time after pilocarpine stimulation, and salt concentration in the sweat depends upon the rate of sweat formation in the individual.
Although a device of this kind might seem to offer advantages over other sweat-collection devices, its limitations preclude practical application other than the experimental use described.